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Purpose: To evaluate a new cultivated coral graft (CCG) in an in vivo experimental guided bone regeneration (GBR) procedure. Materials and Methods: The calvarias of eight rabbits were surgically exposed, and circular defects 8 mm in diameter were prepared. One defect was filled with CCG particles (experimental group); the contralateral defect (control group) was spontaneously filled by blood clot. All defects were covered with a collagen membrane. Subjects were euthanized after 8 weeks. Results: Histologic observations of the defects showed similar bone growth patterns in both experimental and control osteotomies. In the experimental defects, no traces of coral particles were observed. Histometric analysis showed denser bone in the pristine zone (65%-66%) than in the peripheral zone for both the control (50%) and experimental defects (31%) (P = not significant). The new bone percentage was reduced from the peripheral zone toward the middle and the center of the defect (31%, 32%, and 27%, respectively) as the distance from the peripheral pristine bone borders increased. Conclusions: The existing data supports the complete degradation of CCG as a space-maintaining scaffold for GBR procedures. [ABSTRACT FROM AUTHOR]

Postural assessments of the lumbar spine lack valuable information about its properties. The purpose of this study was to assess neutral zone (NZ) characteristics via in vivo lumbar spine passive stiffness and relate NZ characteristics to standing lumbar lordosis. A comparison was made between those that develop low back pain during prolonged standing (pain developers) and those that do not (nonpain developers). Twenty-two participants with known pain status stood on level ground, and median lumbar lordosis angle was calculated. Participants were then placed in a near-frictionless jig to characterize their passive stiffness curve and location of their NZ. Overall, both pain developers and nonpain developers stood with a lumbar lordosis angle that was more extended than their NZ boundary. Pain developers stood slightly more extended (in comparison to nonpain developers) and had a lower moment corresponding to the location of their extension NZ boundary. Overall, in comparison to nonpain developers, pain developers displayed a lower moment corresponding to the location of their extension NZ boundary which could correspond to greater laxity in the lumbar spine. This may indicate why pain developers have a tendency to stand further beyond their NZ with greater muscle co-contraction. [ABSTRACT FROM AUTHOR]

This canine in vivo study assessed the effect of recombinant human platelet-derived growth factor (rhPDGF) on the healing of periapical tissues following apical surgery. From a total of 96 premolar teeth, 64 teeth from six beagle dogs (2 years old) were classified as experimental and were randomly assigned to four experimental groups (16 teeth per group). After having the pulp extirpated, leaving teeth open to the oral cavity for 1 week, and sealing with an immediate restorative material for 8 weeks, nonsurgical endodontic treatment was performed. A split-mouth design was used, and intra-animal randomization of treatment sides was applied to the groups as follows: apical curettage + 1.5-mm root-end resection (Group 1); apicoectomy + mineral trioxide aggregate (MTA) root-end filling (Group 2); apicoectomy + MTA root-end filling + rhPDGF (Group 3); and apical curettage + rhPDGF (Group 4). The animals were sacrificed 24 months after apical surgery, and histologic and µCT analyses were performed for bone volume loss (BVL). Group 1 showed partial resolution of the periapical lesions without signs of tissue regeneration (BVL: 49.09 ± 10.97 mm3). Group 2 had minimal bone regeneration and showed cementum reformation in 9 teeth, with no direct attachment to the MTA (BVL: 35.34 ± 10.97 mm3). Group 3 showed regeneration of all damaged apical tissues without direct contact between the cementum and MTA (BLV: 4.51 ± 1.55 mm3). Group 4 showed regeneration of PDL, bone, and cementum and attachment of functional cementum fibers (BVL: 2.82 ± 2.3 mm3). The difference in BVL was statistically significant only for Groups 1 and 2 (P < .05). rhPDGF may help regenerate apical tissue structures following apical surgery. [ABSTRACT FROM AUTHOR]

The nutritional value of dietary meat protein is closely related to its digestion and subsequent fermentation profiles. Therefore, the understanding of its digestion and its metabolic behaviors in the gut in terms of source and thermal processing attracts an interest for academia and industry. This review focuses on the digestion, absorption, metabolism and health-related outcomes of meat protein based on animal models and human trials. As for meat protein source, fish and chicken are generally associated with a better hepatic lipid metabolism, a higher energy metabolism, a lower intestinal excretion of trimethylamine-N-oxide, N-nitroso compounds, lipoperoxides and a higher abundance of Lactobacillus and A. muciniphila than beef and pork. In terms of thermal processing, a moderate heating can induce positive outcomes in digestibility of meat protein for young people, while well-cooked meat is recommended for the elderly to improve postprandial protein utilization. This review expands knowledge that will be essential for the rational selection of meat sources and thermal processing conditions of meat and meat products for optimal nutritional benefits. HIGHLIGHTS: The nutritional value of meat protein is related to its digestion and fermentation. Meat protein source and thermal processing effects are the main focus. Fish and chicken show different metabolic responses with pork and beef. Moderate cooking favors meat protein digestion in young people but not the elderly. [ABSTRACT FROM AUTHOR]

One of the emerging non-digestible oligosaccharide prebiotics is β-mannooligosaccharides (β-MOS). β-MOS are β-mannan derived oligosaccharides, they are selectively fermented by gut microbiota, promoting the growth of beneficial microorganisms (probiotics), whereas the growth of enteric pathogens remains unaffected or gets inhibited in their presence, along with production of metabolites such as short-chain fatty acids. β-MOS also exhibit several other bioactive properties and health-promoting effects. Production of β-MOS using the enzymes such as β-mannanases is the most effective and eco-friendly approach. For the application of β-MOS on a large scale, their production needs to be standardized using low-cost substrates, efficient enzymes and optimization of the production conditions. Moreover, for their application, detailed in-vivo and clinical studies are required. For this, a thorough information of various studies in this regard is needed. The current review provides a comprehensive account of the enzymatic production of β-MOS along with an evaluation of their prebiotic and other bioactive properties. Their characterization, structural-functional relationship and in-vivo studies have also been summarized. Research gaps and future prospects have also been discussed, which will help in conducting further research for the commercialization of β-MOS as prebiotics, functional food ingredients and therapeutic agents. [ABSTRACT FROM AUTHOR]

A series of 1‐(piperazin‐1‐yl)‐2‐((5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)thio)ethan‐1‐one derivatives (9a–l) were prepared using a multistep reaction between 2‐chloro‐1‐(piperazin‐1yl)ethan‐1‐one derivatives (4a–l) and 5‐(pyridine‐4‐yl)‐1,3,4‐oxadiazole‐2‐thiol (8) and studied their diuretic potential by following established in vivo and in silico protocols. The data obtained from the experimental rat animal model in vivo diuretic studies indicated that synthesized derivatives 9d, 9e, 9g, 9i, and 9j possess excellent diuretic potential. The results obtained from in vivo study were also reinforced by the data of in silico studies performed using AutoDock (1.5.7) software. The molecular docking involved interactions of synthesized molecules with two target proteins, that is, human carbonic anhydrase II protein (hCA‐II, PDB ID: 3HS4) and human NKCCl K289NA492E protein (NKCCl, PDB ID: 7S1Y). The ADME properties of the synthesized molecules have also been determined using pkCSM software that established that the synthesized molecules are good candidates for oral absorption. All the data of in vivo and in silico studies synergized the results that state that the diuretic activity of all synthesized compounds is greater than that of the standard drug (furosemide), whereas compounds 9d, 9e, 9g, 9i, and 9j show excellent activity with values of 1.32, 1.33, 1.35, 1.39, and 1.35, respectively. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc degeneration (IDD) was the most common cause of low back pain. Platelet rich plasma (PRP) has the potential to repair IDD, however, there is still no conclusion on whether Leukocyte-poor platelet rich plasma (Lp-PRP) or Leukocyte-rich platelet rich plasma (Lr-PRP) is better for the treatment of IDD. Methods: First, we conducted an in vitro study to compare the effects of autologous Lp-PRP and Lr-PRP on human degenerated nucleus pulposus (NP) cells. Then we verified the in vivo effects of autologous Lp-PRP and Lr-PRP in treating disc degeneration through a rabbit IDD model. Results: The in vitro study showed both autologous Lp-PRP and Lr-PRP can promote the cell proliferation, the synthesis of COL II and Aggrecan of human degenerated NP cells, while Lp-PRP are better than Lr-PRP (P<0.05). In addition, only Lp-PRP can inhibit the apoptosis of human degenerated NP cells (P<0.05), whereas Lr-PRP activates the catabolism on the contrary (P<0.05). Further, the in vivo study through the rabbit IDD model verified that autologous Lp-PRP has better effects than autologous Lr-PRP in repairing IDD according to X-ray, MRI, histological, and immunohistochemical assessment (P<0.05, respectively). And the caspase-3 IHC results also showed that only autologous Lp-PRP treatment could inhibit apoptosis of NP cells in the rabbit IDD model (P<0.05). Conclusion: Combining in vivo and in vitro studies, the present study confirmed that autologous Lp-PRP has a better effect than autologous Lr-PRP in repairing IDD, which may be due to the inflammatory factors (TNFα, IL-1β, etc.) in Lr-PRP antagonizing part of the repair effects and promoting the catabolism additionally. Therefore, our findings suggest that Lp-PRP may provide better results than Lr-PRP for treating IDD. Further randomized clinical trials will provide evidence to guide practice. [ABSTRACT FROM AUTHOR]

Age-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction. The olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. A decline in olfaction is also associated with early symptoms of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). However, the underlying reasons are unclear. The microphthalmia-associated transcription factor (MITF) is expressed in the projection neurons (PNs) of the OB–the mitral and tufted (M/T) cells. Primary M/T cells from Mitf mutant mice show hyperactivity, potentially attributed to the reduced expression of a key potassium channel subunit, Kcnd3 /Kv4.3. This influences intrinsic plasticity, an essential mechanism involving the non-synaptic regulation of neuronal activity. As neuronal hyperactivity often precedes neurodegenerative conditions, the current study aimed to determine whether the absence of Mitf causes degenerative effects during aging. Aged Mitf mutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OBs of aged Mitf mi-vga9/mi-vga9 mice suggests that during aging, compensatory mechanisms lead to stabilization. [ABSTRACT FROM AUTHOR]

Background: Breast cancer seriously affects physical and mental health of women. Despite advances in the clinical use of different treatments, breast cancer remains a major cause of mortality. Therefore, it is imperative to identify promising treatment options. In the present study, we investigated the effects of shikonin on 4T1 breast cancer cells and its potential mechanisms of action. Methods: BALB/c-derived mouse breast cancer 4T1 is very close to human breast cancer in growth characteristics and systemic response, so 4T1 cells were selected for further experiments. Cell viability, apoptosis, intracellular reactive oxygen species (ROS), mitochondrial activity, and cellular calreticulin (CRT) exposure were assessed to evaluate the antitumor effects and mechanisms of shikonin in vitro. Orthotopic tumor growth inhibition and splenic immune cell regulation by shikonin were evaluated in 4T1 breast cancer orthotopic mice in vivo. Results: In vitro, shikonin could inhibit cell proliferation, cause apoptosis, disrupt mitochondrial activity, and induce ROS production and CRT exposure. In vivo, shikonin inhibited tumor growth, increased the proportion of CD8+ T cells, and reduced the proportion of regulatory cells (CD25+ Foxp3+ T cells) in the spleen. Conclusions: Shikonin inhibits the growth of 4T1 breast cancer cells by disrupting mitochondrial activity, promoting oxidative stress, and regulating immune function. [ABSTRACT FROM AUTHOR]

The procedure of anterior cruciate ligament (ACL) allograft preparation can be divided into fresh-frozen method (FF-allograft) or freeze-dried method (FD-allograft). This study aims to biomechanically and histologically compare the graft to bone tunnel integration between the two allografts. In-vitro results indicated that FF-allograft and FD-allograft showed excellent biocompatibility and biomechanics, while FD-allograft showed a denser collagen fiber arrangement than FF-allograft and autograft. Then, in-vivo preformation of the FF-allograft, FD-allograft, and autograft on bone tunnel integration was evaluated via a canine ACL reconstruction model. In-vivo results indicated that no signs of infection or osteoarthritis were shown in the femur-graft-tibia complexes, but more vascularity and synovitis formed around the implanted FF-allograft. Micro-computed tomography showed that peri-graft bone in the FF-allograft group was significantly increased and remodeled compared with the FD-allograft group; Histologically, the FF-allograft group exhibited similar graft-bone tunnel healing to the FD-allograft group. Tartrate-resistant acid phosphatase (TRAP) staining showed significantly more osteoclasts presented in the FD-allograft group compared to the FF-allograft group. Meanwhile, a significantly higher failure load was shown in the FF-allograft group when compared with the FD-allograft group (P < 0.05). In conclusion, the FF-allograft integrated more firmly into the bone tunnel than the FD-allograft when used in ACL reconstruction. [ABSTRACT FROM AUTHOR]

Carbamazepine is a pharmacological medication commonly prescribed to treat epilepsy. Dose adjustments, poor bioavailability, and prolonged side effects present significant challenges associated with its use. Poloxamer micelles have demonstrated exceptional properties as nanocarriers for drug delivery. This research aimed to develop Poloxamer nanomicelles containing carbamazepine and assess their potential to cross the blood–brain barrier. Poloxamer 407 and P-85 micelles, anchored with TAT as a ligand and containing carbamazepine, were prepared. The morphology, entrapment efficiency, drug release, stability, and toxicity of nanomicelles were examined, along with animal studies conducted to evaluate their anticonvulsant effects. The distribution of carbamazepine-Poloxamer in the brain and plasma was assessed. The results indicated the successful formation of spherical nanomicelles with an average size of less than 100 nm, and carbamazepine was effectively incorporated into the micelles. Formulations composed of mixtures of Poloxamer exhibited a high encapsulation efficiency of approximately 92.1% and remained stable for three months. A sustained release of carbamazepine was observed for up to 72 h. The anticonvulsant effect of carbamazepine-loaded nanomicelles in mice was found to be significantly greater than that of those treated with carbamazepine solution, with the effect increasing by approximately tenfold. Compared to free carbamazepine, the carbamazepine-loaded nanomicelles exhibited a 5.5-fold increase in the brain targeting index, with no toxicity observed in mice treated with these nanomicelles. These findings suggest that Poloxamer micelles represent a promising nanoscale, controlled-release delivery system that is free from toxicity and can enhance the penetration of carbamazepine into the brain while improving its anticonvulsant activity. [ABSTRACT FROM AUTHOR]

Identifying the function and composition of the protein corona (i.e., the set of host proteins interacting with nanoparticles) is considered a crucial step in the development of nanoparticles for medical and pharmacological applications. Evidence suggests that host proteins can alter NP stability, biocompatibility, and pharmacokinetics features. Therefore, in this review, we provide an updated conceptual, methodological, and experimental guideline for the study of the NP protein corona. We surveyed recent literature (2009–2024) focusing on in vitro and in vivo studies. We show that several methods, including shot-gun proteomics, protein identification after in-gel digestion, and TMT proteomics, must be carefully applied and integrated to shed light on this complex phenomenon. Hence, we discuss in detail the relative protocols, highlighting the importance of the experimental conditions, ranging from the administration route to basic, but determinant, parameters like the kind of biological host fluids, the incubation times and the NP concentrations. Additionally, we propose a series of protocols that involve studying the protein corona using purified serum or plasma proteins, as well as sera depleted of specific complement proteins, to investigate the role of their deposition on the nanoparticle surface. We also explore how the role of the protein corona in inducing uptake by phagocytic cells can be examined; finally, we discuss several methodological approaches to study the effects of different coatings on the composition of the protein corona. Available data indicated that it is possible to characterize and punctually study the differential adsorption of specific proteins onto the nanoparticle surface. This allows designing NP chemical coatings features to actively guide the protein corona formation, thus improving nanotheranostic development. [ABSTRACT FROM AUTHOR]

In yeast, control of sulfur amino acid metabolism relies upon Met4 , a transcription factor that activates the expression of a network of enzymes responsible for the biosynthesis of cysteine and methionine. In times of sulfur abundance, the activity of Met4 is repressed via ubiquitination by the SCF Met30 E3 ubiquitin ligase, but the mechanism by which the F-box protein Met30 senses sulfur status to tune its E3 ligase activity remains unresolved. Herein, we show that Met30 responds to flux through the trans-sulfuration pathway to regulate the MET gene transcriptional program. In particular, Met30 is responsive to the biological gas hydrogen sulfide, which is sufficient to induce ubiquitination of Met4 in vivo. Additionally, we identify important cysteine residues in Met30 's WD-40 repeat region that sense the availability of sulfur in the cell. Our findings reveal how SCF Met30 dynamically senses the flow of sulfur metabolites through the trans-sulfuration pathway to regulate the synthesis of these special amino acids. [ABSTRACT FROM AUTHOR]

Objective: Hepatocellular carcinoma (HCC) is a highly lethal cancer with significant mortality, primarily attributed to metastasis. Although Protocadherin Gamma Subfamily A, 9 (PCDHGA9) has been identified as a tumor suppressor gene in cancer metastasis, its role in HCC remains ambiguous. This study clarifies the role of PCDHGA9 in HCC by examining its expression, clinical significance, and molecular activities. Methods: Tissue microarray immunofluorescence analysis evaluated the expression of PCDHGA9 and its clinical relevance. In vitro experiments involved manipulating PCDHGA9 levels in SK-HEP-1 cells to assess migration through wound-healing and transwell assays. In vivo, shPCDHGA9 cell injections were utilized to observe effects on tumor growth and metastasis. Protein analysis and Western Blot validated epithelial-mesenchymal transition (EMT)-related proteins. Subsequent to TGF-β treatment, cell proliferation and apoptosis were quantified using cell counting kit-8 and flow cytometry, respectively, followed by investigation of TGF-β effects on PCDHGA9 N6-methyladenosine (m6A) modification via Methylated RNA immunoprecipitation, RT-qPCR, and Western blot analysis. Results: Downregulation of PCDHGA9 expression in HCC tissues is correlated with poor prognosis. In vitro experiments demonstrated that modulating PCDHGA9 expression influenced HCC cell migration. In vivo, PCDHGA9 knockdown is correlated with increased metastasis. Furthermore, TGF-β stimulation promoted cell proliferation and inhibited apoptosis. Mechanistically, TGF-β-mediated m6A modification led to PCDHGA9 decay, promoting EMT in HCC cells. Conclusion: PCDHGA9 serves as a potential tumor suppressor in HCC by inhibiting EMT. During this process, TGF-β is observed to exert regulatory control over m6A modifications of PCDHGA9. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the zinc finger transcription factor 281 (ZNF281)/ZBP-99 protein has been shown to promote tumor progression, its role in the development of cervical cancer remains unclear. We find that its level is higher in cervical cancer tissues than in normal cervical tissues. And it promotes metastasis in HeLa cell lines by facilitating the epithelial-mesenchymal transition process, thereby enhancing the migration of HeLa cells in vivo. Our research might provide a new marker for predicting the development of cervical cancer. Background: Cervical cancer is the fourth most common cancer among women worldwide. The zinc finger transcription factor 281 (ZNF281)/ZBP-99 protein specifically binds to GC-rich DNA sequences and regulates gene expression, and it has been shown to promote tumor progression. In this study, we aim to investigate the function and molecular mechanism of ZNF281 in uterine cervical carcinoma. Methods: We conducted immunohistochemistry and Western blot assays to determine the expression of ZNF281 in eight human cervical cancer tissues. And, xenograft experiments involving the injection of HeLa cells into nude mice was used to determine the function of ZNF281 on proliferation. Transwell assays were used to detect the migration and invasion of HeLa cells after indicated that ZNF281 overexpression. Results: Our results indicated that ZNF281 protein levels were higher in cervical cancer tissues compared to normal cervical tissues. Additionally, ZNF281 was expressed in human cervical carcinoma cell lines, including HeLa, SiHa, C-33 A, CaSki, and HT-3, and is localized in both the cell nucleus and cytoplasm. ZNF281 overexpression did not influence HeLa cell proliferation or tumor size in situ. Moreover, nude mice injected with ZNF281-overexpressing cell lines developed more tumor lesions in the lungs compared to those injected with control cell lines. Conclusions: These findings suggest that ZNF281 is associated with tumor metastasis without affecting cell proliferation, both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Simple Summary: Various cancer therapies are often ineffective for advanced metastatic liver disease. While immunotherapy can be effective in some cases, it does not provide significant benefits for metastatic cancer in the liver. CBL0137 is an experimental drug that helps form a special type of DNA called Z-DNA, which may help boost the body's immune response against tumors. We investigated how CBL0137 affects metastatic liver tumor models from colon (CT26) and breast (4T1) cancers focusing on how it triggers immune responses. The results showed that CBL0137 hepatic arterial infusion (HAI) enhanced anti-tumor effects by depleting immune-suppressing cells while preserving effector T cells. Combining CBL0137 HAI with conventional immunotherapy improved survival in 4T1 tumors but not in CT26 tumors, highlighting the importance of targeting specific immune cell populations for effective treatment. Background: Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. Methods: Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. Results: CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. Conclusions: Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: STING agonists face challenges in breast cancer treatment due to their lower accumulation in tumors and rapid clearance from the body, resulting in a short duration of therapeutic effect. Novel phase-transitional liposomes loaded with STING agonists have been developed to overcome these limitations and are specifically designed for low-intensity focused ultrasound (LIFU)-assisted molecular imaging and precise treatment of breast cancer. With the assistance of LIFU, iRGD-modified liposomes (a targeting peptide) undergo a phase transition into microbubbles, leading to enhanced ultrasound molecular imaging of tumors and facilitating breast cancer immunotherapy by releasing STING agonists from the ultrasound-targeted liposomes. Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system's ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is the deadliest form of primary brain cancer, and the survival of patients is only about 15 months after diagnosis, even with aggressive treatment. Many cellular factors that are used by GBM cells to divide abnormally and invade brain tissue to result in patient death are unknown. Here, we investigated the potential role of the cellular enzyme QSOX1, which creates specific bonds within proteins, in GBM cell proliferation, migration in a dish, and invasion into brain tissue in our chick embryo brain tumor model system. By experimentally reducing QSOX1 protein production in GBM cells, we found that this reduction resulted in less proliferation, slower migration, and less invasion into brain tissue. These results show the importance of the QSOX1 enzyme in GBM cells in order for them to exhibit their abnormal aggressive behavior that drives this incurable cancer. Background: Quiescin Sulfhydryl Oxidase 1 (QSOX1) is an enzyme that catalyzes the oxidation of free thiols to generate disulfide bonds in a variety of proteins, including the cell surface and extracellular matrix. QSOX1 has been reported to be upregulated in a number of cancers, and the overexpression of QSOX1 has been correlated with aggressive cancers and poor patient prognosis. Glioblastoma (GBM) brain cancer has been practically impossible to treat effectively, with cells that rapidly invade normal brain tissue and escape surgery and other treatment. Thus, there is a crucial need to understand the multiple mechanisms that facilitate GBM cell invasion and to determine if QSOX1 is involved. Methods and Results: Here, we investigated the function of QSOX1 in human glioblastoma cells using two cell lines derived from T98G cells, whose proliferation, motility, and invasiveness has been shown by us to be dependent on disulfide bond-containing adhesion and receptor proteins, such as L1CAM and the FGFR. We lentivirally introduced shRNA to attenuate the QSOX1 protein expression in one cell line, and a Western blot analysis confirmed the decreased QSOX1 expression. A DNA content/cell cycle analysis using flow cytometry revealed 27% fewer knockdown cells in the S-phase of the cell cycle, indicating a reduced proliferation. A cell motility analysis utilizing our highly quantitative SuperScratch time-lapse microscopy assay revealed that knockdown cells migrated more slowly, with a 45% decrease in migration velocity. Motility was partly rescued by the co-culture of knockdown cells with control cells, indicating a paracrine effect. Surprisingly, knockdown cells exhibited increased motility when assayed using a Transwell migration assay. Our novel chick embryo orthotopic xenograft model was used to assess the in vivo invasiveness of knockdown vs. control cells, and tumors developed from both cell types. However, fewer invasive knockdown cells were observed after about a week. Conclusions: Our results indicate that an experimental reduction in QSOX1 expression in GBM cells leads to decreased cell proliferation, altered in vitro migration, and decreased in vivo invasion. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer represents a main public health issue around the world due to the mortality rates associated with it, the lack of effective and potent drugs, the multitude of side effects and the expensive treatments. Until now, no natural alternative therapeutic methods have been found beneficial enough to replace conventional drugs. Thus, bioactive compounds with anticancer properties can represent a necessary alternative through a targeted molecular approach to the multiple pathways involved in carcinogenesis. This review explores how the therapeutic potential of natural compounds can be harnessed and how they can be used as adjuvant therapies for oral cancer treatment. The collected results focused only on plant extracts and biologically active metabolites known for their antioxidant, anti-inflammatory and antitumor potential, which can be described as future chemopreventive agents against oral cancer, alone or in therapeutic combinations. Background: With a significant increase in both incidence and mortality, oral cancer—particularly oral squamous cell carcinoma (OSCC)—is one of the main causes of death in developing countries. Even though there is evidence of advances in surgery, chemotherapy, and radiotherapy, the overall survival rate for patients with OSCC has improved, but by a small percentage. This may be due, on the one hand, to the fact that the disease is diagnosed when it is at a too-advanced stage, when metastases are already present. Methods: This review explores the therapeutic potential of natural herbal products and their use as adjuvant therapies in the treatment of oral cancer from online sources in databases (PubMed, Web of Science, Google Scholar, Research Gate, Scopus, Elsevier). Results: Even if classic therapies are known to be effective, they often produce many serious side effects and can create resistance. Certain natural plant compounds may offer a complementary approach by inducing apoptosis, suppressing tumor growth, and improving chemotherapy effectiveness. The integration of these compounds with conventional treatments to obtain remarkable synergistic effects represents a major point of interest to many authors. This review highlights the study of molecular mechanisms and their efficiency in in vitro and in vivo models, as well as the strategic ways in which drugs can be administered to optimize their use in real contexts. Conclusions: This review may have a significant impact on the oncology community, creating new inspirations for the development of more effective, safer cancer therapies with less toxic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy remains a central pillar in the therapy of solid tumors, including lung cancer. However, the clinically applied radiation dose to a lung tumor is limited by the radiation-sensitivity of the surrounding normal tissue such as the lungs and heart. Ionizing irradiation causes reactive oxygen species (ROS)-induced chronic vascular inflammation, which can result in fatal irradiation-induced lung diseases such as pneumonitis and fibrosis. In this study, we demonstrate that cannabidiol (CBD), the non-psychogenic component of cannabis, mediates anti-inflammatory and anti-oxidative effects that protect the microvasculature of the lung against radiation-induced damage using in vitro and in vivo murine models. CBD therefore has the potential to improve the clinical outcome of radiotherapy by reducing normal tissue toxicity in the lung. Objective: Radiotherapy, which is commonly used for the local control of thoracic cancers, also induces chronic inflammatory responses in the microvasculature of surrounding normal tissues such as the lung and heart that contribute to fatal radiation-induced lung diseases (RILDs) such as pneumonitis and fibrosis. In this study, we investigated the potential of cannabidiol (CBD) to attenuate the irradiation damage to the vasculature. Methods: We investigated the ability of CBD to protect a murine endothelial cell (EC) line (H5V) and primary lung ECs isolated from C57BL/6 mice from irradiation-induced damage in vitro and lung ECs (luECs) in vivo, by measuring the induction of oxidative stress, DNA damage, apoptosis (in vitro), and induction of inflammatory and pro-angiogenic markers (in vivo). Results: We demonstrated that a non-lethal dose of CBD reduces the irradiation-induced oxidative stress and early apoptosis of lung ECs by upregulating the expression of the cytoprotective mediator heme-oxygenase-1 (HO-1). The radiation-induced increased expression of inflammatory (ICAM-2, MCAM) and pro-angiogenic (VE-cadherin, Endoglin) markers was significantly reduced by a continuous daily treatment of C57BL/6 mice with CBD (i.p. 20 mg/kg body weight), 2 weeks before and 2 weeks after a partial irradiation of the lung (less than 20% of the lung volume) with 16 Gy. Conclusions: CBD has the potential to improve the clinical outcome of radiotherapy by reducing toxic side effects on the microvasculature of the lung. [ABSTRACT FROM AUTHOR]

Simple Summary: Somatostatin, a growth hormone-release-inhibiting peptide (SST/SRIF), is a widely distributed multifunctional cyclic peptide that acts by activating G protein-coupled receptors (SSTRs, SST1-5). The diagnostic and prognostic role of these peptides in sporadic CRC remains unclear. The current study showed significant differences in the expression of SST and all SSTRs in the tissue material of sporadic CRC, control colorectal mucosa, and in lymph node metastases from the same patients. A significant dependence of the immunoexpression of SST1-5 on the cellular localization pattern was proved. Differences and/or significant correlations of SRIF system components with clinicopathological data (age, histological subtype of CRC, TNM parameters, Ki-67 antigen, and laboratory tests) were found. Interestingly, only control tissue showed differences in SST1-5 expression depending on the colon segment. The coexpression of all SST1-5 and overexpression of not only SST2 and SST5 in CRC may have applications for future therapy based on the SRIF system in sporadic CRC. Background/Objectives: Colorectal cancer (CRC) is one of the most common human malignancies worldwide. The somatotropin-releasing inhibitory factor/somatostatin (SRIF/SST) acts through activation of five membrane receptors (SSTRs, SST1-5). The diagnostic and prognostic role of these peptides in sporadic CRC remains unclear. This study aimed to determine the role of tissue expression of SST and all SSTRs in the pathogenesis, diagnosis, and prognosis of sporadic CRC. Methods: The expression of SST and all SSTRs was assessed in the tissues of CRC patients, control colorectal mucosa and lymph node metastasis from the same patients using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Results: Decreased SST (mRNA and peptide) and higher SST2 and SST5 (mRNA and peptide) expression in CRC vs. control was noted. A negative correlation between SST mRNA expression and patient's age in CRC and control groups were observed. IHC study confirmed the coexpression of SSTRs in all tissue groups and significant dependence on the cellular localization. Immunoexpression of SST2 and SST3 showed the most correlations with clinicopathological data in CRC patients. Interestingly, only control tissue showed differences in SST1-5 expression depending on the colon segment. Conclusions: Reduced SST expression in CRC indicates a weakening in its antitumor effect in this cancer in vivo. Overexpression of SST2 and SST5 in CRC suggests that these receptors play an important role in the pathogenesis of this cancer. Analysis of SST1-5 tissue expression allows for differentiation between the mucinous and nonmucinous CRC subtypes. The coexpression of all SST1-5 and overexpression of not only SST2 and SST5 in CRC may have applications for future therapy based on the SRIF system in sporadic CRC. [ABSTRACT FROM AUTHOR]

Background: Distal femoral varus osteotomy (DFVO) is an established surgical procedure for addressing valgus malalignment across various knee conditions. However, the effect of DFVO on stress distribution within the femorotibial joint has not been explored through in vivo studies. Purpose: To (1) explore the distribution pattern of subchondral bone density across the proximal tibia in nonarthritic knees without arthritis and in those of patients with valgus knees, (2) assess changes in the pattern of bone density distribution in patients with valgus knees before and after medial closing-wedge (MCW) DFVO, and (3) determine the correlation between leg alignment and changes in bone density distribution. Study Design: Cohort study; Level of evidence, 3. Methods: The authors retrospectively analyzed clinical and radiographic data from 14 patients (14 knees; mean age, 44 years; 3 men, 11 women) treated with MCW-DFVO for lateral compartment osteoarthritis (OA) due to valgus malalignment, alongside a control group of 18 patients (18 knees; mean age, 21 years; 4 men, 14 women) without OA. The distribution patterns of subchondral bone density distribution on the femorotibial articular surface of the tibia were examined both preoperatively and >1 year postoperatively using computed tomography osteoabsorptiometry. Quantitative analyses were conducted on the locations and percentages of the high-density areas (HDAs) on the articular surface. The mean time between surgery and the postoperative radiograph and computed tomography absorptiometry imaging was 13.6 months (range, 11-19 months). The mean length of clinical follow-up was 28.7 months (range, 14-62 months) after surgery. Results: The mean proportion of HDA in the lateral compartment relative to the total HDA (lateral ratio) was significantly greater in the preoperative OA group (58.8%) compared with the control group (41.1%) (P <.001). After MCW-DFVO, the mean lateral ratio in the OA group notably declined to 45.3% (P <.001). The lateral ratio exhibited a significant correlation with the hip-knee-ankle angle in both the control (r = 0.630; P =.011) and OA (r = 0.537; P =.047) groups. Moreover, the alteration in the lateral ratio after MCW-DFVO showed a significant relationship with changes in the hip-knee-ankle angle (r = 0.742; P =.002) and the mechanical lateral distal femoral angle (r = −0.752; P =.002). Within the lateral compartment, HDAs in the 3 lateral regions of the 4 lateral subregions diminished after MCW-DFVO, whereas in the medial compartment, HDAs in the 3 lateral subregions saw an increase. Conclusion: The mean lateral ratio was significantly greater in the preoperative OA group compared with the control group. MCW-DFVO resulted in a redistribution of HDA from the lateral to the medial compartment of the proximal tibial articular surface. The extent of alignment correction after MCW-DFVO was closely linked to the shifts in HDA distribution, reflecting changes in stress distribution. [ABSTRACT FROM AUTHOR]

Our aim in the current study was to determine the in vitro and in vivo synergistic antiinflammatory and antiallergic effect associated with the IL-12 production of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC) and ILS-F-2301 (2:8 extract of Psidium guajava and Camellia sinensis). Compared to EGCG alone, GEC showed synergistic inhibition of nitric oxide (NO), inducible NO synthase, and cyclooxygenase-2 by 3.8, 5.1, and 4.1%, respectively. The downregulation of interleukin-12 (IL-12) by 2,4-dinitrophenyl-human serum albumin conjugate/DNP-immunoglobulin E or ovalbumin (OVA) was synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of downregulation of IL-12 in plasma increased by 100 mg/kg with ILS-F-2301 (28.7%) when compared to the OVA/Alu-treated group. Also, GEC synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of down and cyclooxygenase C synergistically inhibited p-Akt, PI3K, mTOR, p-STAT6, and GATA3 by 4.9%, 4.1%, 19.2%, 23.8%, and 35.3%, respectively, while increasing the expressions of p-STAT1 and T-bet (showing 53.3% and 9.4% activation) when compared to EGCG alone. In an allergenic rhinitis mouse model, 100 mg/kg of ILS-F-2301 was shown to inhibit p-Akt, PI3K, mTOR, p-c-Jun N-terminal kinase (p-JNK), p-extracellular signal-regulated kinase (p-ERK), and p-p38 by 23.3%, 43.8%, 17.2%, 32.2%, 29.1%, and 41.8% when compared to the OVA/Alu-sensitized group. Taken together, our findings suggest that ILS-F-2301 may have potential as a functional food for alleviating antiallergic rhinitis. [ABSTRACT FROM AUTHOR]

Purpose: The radionuclide pair cerium-134/lanthanum-134 (134Ce/134La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (225Ac). The unique properties of 134Ce offer perspectives for developing innovative in vivo investigations that are not possible with 225Ac. In this work, 225Ac- and 134Ce-labelled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation. Despite being an excellent chemical match, 134Ce/134La has limitations to the setting of quantitative positron emission tomography imaging. Methods: The precursor PSMA-617 and a macropa-based tetrazine-conjugate (mcp-PEG8-Tz) were radiolabelled with 225Ac or 134Ce and compared in vitro and in vivo using standard (radio)chemical methods. Employing biodistribution studies and positron emission tomography (PET) imaging in athymic nude mice, the radiolabelled PSMA-617 tracers were evaluated in a PC3/PIP (PC3 engineered to express a high level of prostate-specific membrane antigen) prostate cancer mouse model. The 225Ac and 134Ce-labelled mcp-PEG8-Tz were investigated in a BxPC-3 pancreatic tumour model harnessing the pretargeting strategy based on a trans-cyclooctene-modified 5B1 monoclonal antibody. Results: In vitro and in vivo studies with both 225Ac and 134Ce-labelled tracers led to comparable results, confirming the matching pharmacokinetics of this theranostic pair. However, PET imaging of the 134Ce-labelled precursors indicated that quantification is highly dependent on tracer internalization due to the redistribution of 134Ce's PET-compatible daughter 134La. Consequently, radiotracers based on internalizing vectors like PSMA-617 are suited for this theranostic pair, while slow-internalizing 225Ac-labelled tracers are not quantitatively represented by 134Ce PET imaging. Conclusion: When employing slow-internalizing vectors, 134Ce might not be an ideal match for 225Ac due to the underestimation of tumour uptake caused by the in vivo redistribution of 134La. However, this same characteristic makes it possible to estimate the redistribution of 225Ac's progeny noninvasively. In future studies, this unique PET in vivo generator will further be harnessed to study tracer internalization, trafficking of receptors, and the progression of the tumour microenvironment. [ABSTRACT FROM AUTHOR]

Techniques to study splicing kinetics include metabolic labeling time courses, 3′ splice site-RNA polymerase II distance-based measurements, and microscopy-based methods. The global median splicing time is of the order of minutes in many organisms, including yeast, Drosophila , and humans. Many instances of splicing events occurring on the order of seconds have also been observed. Single intron excision kinetics are highly variable. Many molecular features are associated with splicing kinetics, including intron length, the distance of an intron from its respective gene boundaries, and whether a splicing event is alternative or constitutive. Splicing is a highly regulated process critical for proper pre-mRNA maturation and the maintenance of a healthy cellular environment. Splicing events are impacted by ongoing transcription, neighboring splicing events, and cis and trans regulatory factors on the respective pre-mRNA transcript. Within this complex regulatory environment, splicing kinetics have the potential to influence splicing outcomes but have historically been challenging to study in vivo. In this review, we highlight recent technological advancements that have enabled measurements of global splicing kinetics and of the variability of splicing kinetics at single introns. We demonstrate how identifying features that are correlated with splicing kinetics has increased our ability to form potential models for how splicing kinetics may be regulated in vivo. [ABSTRACT FROM AUTHOR]

The current work aims to develop a bigel-containing clobetasol propionate-loaded PLGA microparticles and further assess its in vitro, ex vivo, and in vivo behavior for psoriasis management. PLGA microparticles (2%w/w) containing clobetasol propionate were developed by solvent evaporation technique. For the developed particles, size, drug loading, entrapment efficiency, and surface morphology were determined. Further, the particles were suspended into bigel developed from oleogel and hydrogel (40:60) and assessed for stability, in vitro drug release, ex vivo skin permeation, retention, and in vivo study in BALB c mice for antipsoriatic potential. PLGA microparticles developed by solvent evaporation were found to have a mean particle size of 19.45 ± 1.74 μm. Drug loading and entrapment efficiency for clobetasol were found to be 43.5 ± 4.94% and 94.5 ± 3.68%, respectively. For the developed bigel, sustained in vitro drug release was observed till 7 h. Ex vivo skin permeation with the developed formulation was found to be higher than the marketed formulation and drug suspended in bigel. A retention study performed on pig skin suggested the topical skin retention of the drug. Further, the psoriatic model was developed in BALB c mice with IMQ cream, and it was observed that the developed formulation helped considerably reduce the irritation score and PASI scoring in mice as compared to the standard treatment. The same is corroborated with the help of histopathological studies performed by Hematoxylin and Eosin (H&E) staining in the same animals. The study findings suggest that clobetasol microparticle-loaded bigel formulation appeared to be a promising therapy option for psoriasis. [ABSTRACT FROM AUTHOR]

Objective: Autoinflammation and phospholipase C (PLC) γ2–associated antibody deficiency and immune dysregulation (APLAID) syndrome is an autoinflammatory disease caused by gain‐of‐function variants in PLCG2. This study investigates the pathogenic mechanism of a novel variant of PLCG2 in a patient with APLAID syndrome. Methods: Whole‐exome sequencing and Sanger sequencing were used to identify the pathogenic variant in the patient. Single‐cell RNA sequencing, immunoblotting, luciferase assay, inositol monophosphate enzyme‐linked immunosorbent assay, calcium flux assay, quantitative PCR, and immunoprecipitation were used to define inflammatory signatures and evaluate the effects of the PLCG2 variant on protein functionality and immune signaling. Results: We identified a novel de novo variant, PLCG2 p.D993Y, in a patient with colitis, pansinusitis, skin rash, edema, recurrent respiratory infections, B‐cell deficiencies, and hypogammaglobulinemia. The single‐cell transcriptome revealed exacerbated inflammatory responses in the patient's peripheral blood mononuclear cells. Expression of the D993Y variant in HEK293T, COS‐7, and PLCG2 knock‐out THP‐1 cell lines showed heightened PLCγ2 phosphorylation; elevated inositol‐1,4,5‐trisphosphate production and intracellular Ca2+ release; and activation of the MAPK, NF‐κB, and NFAT signaling pathways compared with control‐transfected cells. In vitro experiments indicated that the D993Y variant altered amino acid properties, disrupting the interaction between the catalytic and autoinhibitory domains of PLCγ2, resulting in PLCγ2 autoactivation. Conclusion: Our findings demonstrated that the PLCG2 D993Y variant is a gain‐of‐function mutation via impairing its autoinhibition, activating multiple inflammatory signaling pathways, thus leading to APLAID syndrome. This study further broadens the molecular underpinnings and phenotypic spectrum of PLCγ2‐related disorders. [ABSTRACT FROM AUTHOR]

Field hockey is characterized by a unique dribbling position which has been associated with a prevalence of low back pain and lumbar injury. To quantify the biomechanical response of the hockey-specific running gait, twelve field hockey players completed treadmill running at speeds of 6, 9 and 12 km·hr−1 with a normal running gait and whilst manipulating the hockey stick to replicate dribbling. Mechanical loading was quantified using tri-axial accelerometery at L4, and muscular activity was measured for biceps femoris (BF), gluteus medius (GM) and quadratus lumborum (QL) of each limb. Running with the stick elicited greater mechanical loading in the medio-lateral (p = 0.001) and antero-posterior (p = 0.003) planes, and increased peak (p = 0.004) and mean (p = 0.002) EMG response of QL (p = 0.004). The greater planar mechanical loading and QL activation in response to hockey-specific running technique support epidemiological observations of lower back pain prevalence. The sensitivity of uni-axial mechanical loading to the hockey-specific running posture provides an efficacious means of objectively monitoring mechanical loading in-vivo, whilst the QL activation response has implications for (p)rehabilitative interventions. Running posture and speed can be considered as discrete progressions when considering training load. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) is a non-psychotropic cannabinoid with multiple pharmacological properties. Cannabidiol has attracted growing attention in the cosmetic industry, with an increasing number of CBD-containing skincare products on the market in recent years. The aim of this review is to evaluate the current evidence on the use of CBD for cosmetic purposes. Following an overview of CBD and the endocannabinoid system in the skin, we summarize pre-clinical and clinical studies that address the potential of CBD in cosmetic dermatology. Available in vitro and in vivo evidence suggests that CBD has anti-oxidant, anti-inflammatory, moisturizing, anti-acne, wound-healing, and anti-aging properties. However, only a few clinical studies have been conducted on the use of CBD in the skin. In addition, there is a critical need to develop an efficient drug-delivery system for topical/transdermal application of CBD. Further research, including clinical and pharmacokinetic studies, are needed to fully evaluate the role of CBD in cosmetic dermatology. [ABSTRACT FROM AUTHOR]

In-vitro protein refolding is a major bottleneck step in the large-scale manufacturing of antibody fragments expressed in a microbial host system. The formation of an inter-chain disulfide bond is a key rate-limiting step during in-vitro refolding of antibody fragment therapeutics. In this investigation, we report the use of two redox mutant strains of E. coli viz., SHuffle® T7 (DE3) and SHuffle® T7 Express (DE3) possessing an oxidizing cytoplasm for the soluble expression of a refolded biosimilar antibody fragment. The effect of various critical process parameters on antibody fragment refolding yield was studied using a Design of Experiment (DoE) approach. The optimized upstream processing led to the expression of 167 ± 2.53 mg/L and 95 ± 1.44 mg/L of soluble refolded biosimilar Ranibizumab using the SHuffle® T7 (DE3) and SHuffle® T7 Express (DE3) strains, respectively, at the bioreactor scale. Physicochemical characteristics of the in-vivo refolded antibody fragment were studied and compared with an innovator molecule using various orthogonal analytical methods. A biological activity study of in-vivo refolded Ranibizumab using HUVEC cell-based bioassay proved that cell proliferation inhibition is comparable to the innovator Ranibizumab. The proposed strategy offers a time and cost-effective manufacturing platform for antibody fragments. [Display omitted] • Efficient soluble expression of in-vivo refolded antibody fragment. • Elimination of in-vitro refolding step. • DoE-based optimization of process parameters to enhance soluble target protein yield. • Novel downstream processing platform for the purification of antibody fragments. • Reduction in overall manufacturing time from nine days to three days. [ABSTRACT FROM AUTHOR]

The current study aimed to evaluate the pharmacokinetics and neuroprotective effect of well-characterised berberine-bovine serum albumin (BBR-BSA) nanoparticles. BBR-BSA nanoparticles were generated by desolvation method. Entrapment efficiency, loading capacity, particle size, polydispersity index, surface morphology, thermal stability, and in-vitro release were estimated. In-vitro pharmacokinetic and tissue distribution were conducted. Their neuroprotection was evaluated against lipopolysaccharides-induced neurodegeneration. BBR-BSA nanoparticles showed satisfactory particle size (202.60 ± 1.20 nm) and entrapment efficiency (57.00 ± 1.56%). Results confirmed the formation of spheroid-thermal stable nanoparticles with a sustained drug release over 48 h. Sublingual and intranasal routes had higher pharmacokinetic plasma profiles than other routes, with Cmax values at 0.75 h (444 ± 77.79 and 259 ± 42.41 ng/mL, respectively). BBR and its metabolite distribution in the liver and kidney were higher than in plasma. Intranasal and sublingual treatment improves antioxidants, proinflammatory, amyloidogenic biomarkers, and brain architecture, protecting the brain. In conclusion, neuroinflammation and neurodegeneration may be prevented by intranasal and sublingual BBR-BSA nanoparticles. [ABSTRACT FROM AUTHOR]

Papaya is one of the most consumed fruits around the world, which possesses low energy and is very suitable for those trying to reduce weight. Papaya is packed with a bunch of vitamins, minerals, as well as phenolic compounds. Phytochemicals have beneficial effects on the human body, including anti-cancer, anti-diabetic, and anti-dengue activities. Numerous studies have estimated nutritional and medicinal properties. The study of the bioaccessibility of papaya chemicals is important for both the food and medicine industries. This review summarizes the nutritional value and phytochemical content of different parts of papaya. Influencing factors like pre- and post-harvest on phytochemical content also have been reviewed. Further, the bioaccessibility and bioavailability of phytochemicals as well as the medicinal properties, based on the in vitro and in vivo studies are deeply reviewed. Finally, the research progress, gaps and interesting future aspects of papaya phytochemicals have been discussed. These phytochemical compounds are influenced by numerous factors, such as pre- and post-harvest, as well as extraction conditions. Many factors may affect the bioaccessibility and bioavailability of these phytochemicals, but there is limited information. Therefore, further studies like in vitro and in vivo experiments should be conducted to authenticate the efficiency of the papaya plant. [ABSTRACT FROM AUTHOR]

Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism. [ABSTRACT FROM AUTHOR]

Vitreous, one of the largest components of the human eye, mostly contains water. Despite decades of studying the vitreous structure, numerous unanswered questions still remain, fueling ongoing active research. We attempt to provide a comprehensive overview of the current understanding of the development, morphology, biochemical composition, and function of the vitreous. We emphasize the impact of the vitreous structure and composition on the distribution of drugs. Fast-developing imaging technologies, such as modern optical coherence tomography, unlocked multiple new approaches, offering the potential for in vivo study of the vitreous structure. They allowed to analyze in vivo a range of vitreous structures, such as posterior precortical vitreous pockets, Cloquet canal, channels that interconnect them, perivascular vitreous fissures, and cisterns. We provide an overview of such imaging techniques and their principles and of some challenges in visualizing vitreous structures. Finally, we explores the potential of combining the latest technologies and machine learning to enhance our understanding of vitreous structures. [ABSTRACT FROM AUTHOR]

Background: Iodine is one of the essential trace elements for human life. The main objective of the biofortification of plants with iodine is to obtain food with a higher content of this element compared to conventional food. Biofortification of plants with iodine can increase the intake of this trace element by different populations. In addition, it may reduce the risk of iodine deficiency diseases. Objectives: The aim of the study was to investigate the effect of kale biofortified with 8-hydroxy-7-iodo-5-quinolinesulfonic acid (8-OH-7-I-5QSA) on iodine bioavailability and biochemical effects in Wistar rats. Methods: Kale biofortified with (8-OH-7-I-5QSA) was tested for iodine levels in urine, feces, and selected tissues using the ICP-MS/MS technique. The feeding experiment was designed to investigate potential changes in selected thyroid-regulated biochemical parameters in blood serum of Wistar rats. Results: The dietary intake of Wistar rats fed kale biofortified with (8-OH-7-I-5QSA) from both the "Oldenbor F1" and "Redbor F1" cultivars for 8 weeks resulted in significantly (p ≤ 0.05) higher iodine concentrations in the urine and kidneys of rats, which proves iodine bioavailability. Rats' diets with "Oldenbor F1" and "Redbor F1" kale non- and -biofortified with 8-OH-7-I-5QSA had a significantly (p ≤ 0.05) lower or a tendency for lower concentration of TSH, triglyceride, total and direct bilirubin, TBARs, uric acid, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations in serum. Dietary intake of "Oldenbor F1" and "Redbor F1" kale biofortified with 8-OH-7-I-5QSA significantly (p ≤ 0.05) increased the total antioxidant status (TAS). Conclusions: Our study confirms that kale biofortified with iodine in organic form iodoquinoline 8-OH-7-I-5QSA is bioavailable and well absorbed by the Wistar rat and has a positive effect on selected biochemical parameters. The results obtained in this study may be highly predictive for further studies in humans. [ABSTRACT FROM AUTHOR]

Proton MRS is used clinically to collect localized, quantitative metabolic data from living tissues. However, the presence of baselines in the spectra complicates accurate MRS data quantification. The occurrence of baselines is not specific to short‐echo‐time MRS data. In short‐echo‐time MRS, the baseline consists typically of a dominating macromolecular (MM) part, and can, depending on B0 shimming, poor voxel placement, and/or localization sequences, also contain broad water and lipid resonance components, indicated by broad components (BCs). In long‐echo‐time MRS, the MM part is usually much smaller, but BCs may still be present. The sum of MM and BCs is denoted by the baseline. Many algorithms have been proposed over the years to tackle these artefacts. A first approach is to identify the baseline itself in a preprocessing step, and a second approach is to model the baseline in the quantification of the MRS data themselves. This paper gives an overview of baseline handling algorithms and also proposes a new algorithm for baseline correction. A subset of suitable baseline removal algorithms were tested on in vivo MRSI data (semi‐LASER at TE = 40 ms) and compared with the new algorithm. The baselines in all datasets were removed using the different methods and subsequently fitted using spectrIm‐QMRS with a TDFDFit fitting model that contained only a metabolite basis set and lacked a baseline model. The same spectra were also fitted using a spectrIm‐QMRS model that explicitly models the metabolites and the baseline of the spectrum. The quantification results of the latter quantification were regarded as ground truth. The fit quality number (FQN) was used to assess baseline removal effectiveness, and correlations between metabolite peak areas and ground truth models were also examined. The results show a competitive performance of our new proposed algorithm, underscoring its automatic approach and efficiency. Nevertheless, none of the tested baseline correction methods achieved FQNs as good as the ground truth model. All separately applied baseline correction methods introduce a bias in the observed metabolite peak areas. We conclude that all baseline correction methods tested, when applied as a separate preprocessing step, yield poorer FQNs and biased quantification results. While they may enhance visual display, they are not advisable for use before spectral fitting. [ABSTRACT FROM AUTHOR]

Purpose: T 2$$ {}_2 $$‐weighted turbo‐spin‐echo (TSE) sequences are a fundamental technique in brain imaging but suffer from field inhomogeneities at ultra‐high fields. Several methods have been proposed to mitigate the problem, but were limited so far to nonselective three‐dimensional (3D) measurements, making short acquisitions difficult to achieve when targeting very high resolution images, or needed additional calibration procedures, thus complicating their application. Methods: Slab‐selective excitation pulses were designed for flexible placement utilizing the concept of k T$$ {}_T $$‐spokes. Phase‐coherent refocusing universal pulses were subsequently optimized with the Gradient Ascent Pulse Engineering algorithm and tested in vivo for improved signal homogeneity. Results: Implemented within a 3D variable flip angle TSE sequence, these pulses led to a signal‐to‐noise ratio (SNR) improvement ranging from 10% to 30% compared to a two‐dimensional (2D) T2w TSE sequence employing B1+$$ {\mathrm{B}}_1^{+} $$‐shimmed pulses. B1+$$ {\mathrm{B}}_1^{+} $$ field inhomogeneities could be mitigated and artifacts from B0$$ {\mathrm{B}}_0 $$ deviations reduced. The concept of universal pulses was successfully applied. Conclusion: We present a pulse design method which provides a set of calibration‐free universal pulses (UPs) for slab‐selective excitation and phase‐coherent refocusing in slab‐selective TSE sequences. [ABSTRACT FROM AUTHOR]

Objective: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. Methods: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. Results: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). Conclusion: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the inhibitory effect of Celastrus orbiculatus extracts (COE) on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in vivo. Methods: The 38B9 lymphoma cells were treated with COE (160 µ g/mL) and CTX (25 µ mol/L). The apoptosis rate and cell cycle of each group were detected by flow cytometry. The secretion of inflammatory factors, including interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α), in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). In vivo, BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma model. COE (3 mg·kg−1·d−1) and CTX (40 mg·kg−1·d−1) were administered to the model mice, respectively. The expression of plasma inflammatory factors (IL-6, IL-10 and TNF-α) and thrombus indexes, including D-dimer (D-D), von Willebrand factor (vWF) and tissue factor (TF), were detected by ELISA before tumor bearing (1 d), after tumor formation (14 d) and after intervention (21 d). PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps (NETs). Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2 (CLEC-2). The tumor growth and survival of mice were recorded. Results: The 38B9 lymphoma cells were apoptotic after the intervention of COE and CTX. The ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells (P<0.05), and S phase cells decreased in CTX intervented cells (P<0.05). Also, the secretion level of IL-6 was significantly reduced after COE or CTX intervention (P<0.05), and IL-10 was significantly increased (P<0.05). Furthermore, the tumor mass was reduced, and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in non-intervented mice. The significantly lower levels of TNF-α, IL-6, NETs, TF, DD and CLEC-2, as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice (P<0.05). Conclusion: COE has a mild and stable anti-tumor effect, which can reduce the secretion of inflammatory factors by lymphoma cells and regulate thrombophilic state caused by tumor inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

Olive family (Oleaceae) contains several species among which Olea europaea L. is mostly used for production of olive oils. Various parts of olive tree are rich source of diverse bioactive compounds such as Apigenin, elenolic acid, Hydroxytyrosol, Ligstroside, Oleoside, Oleuropein, Oleuropein aglycone, Tyrosol, etc. Among these, oleuropein, a secoiridoid is predominantly found in olive leaves and young olive fruits of different species of Oleaceae family. Scientists have adopted numerous extraction methods (conventional & latest) to increase the yield of oleuropein. Among these techniques, maceration, soxhlet, microwave-assisted, ultrasonication, and supercritical fluid methods are most commonly employed for extraction of oleuropein. Evidently, this review emphasizes on various in-vitro and in-vivo studies focusing on nutraceutical properties of oleuropein. Available literature highlights the pharmaceutical potential of oleuropein against various diseases such as obesity, diabetes, cardiovascular complications, neurodegenerative diseases, cancer, inflammation, microbial infections, and oxidation. This review will benefit the scientific community as it narrates comprehensive literature regarding absorption, metabolism, bioavailability, extraction techniques, and nutraceutical perspectives associated with oleuropein. [ABSTRACT FROM AUTHOR]

Background: Gallium-68 positron emission tomography (68Ga-PET) with the two registered somatostatin analogs, [68Ga]Ga-DOTA-Tyr3-octreotide ([68Ga]Ga-DOTA-TOC) and [68Ga]Ga-DOTA-Tyr3-octreotate ([68Ga]Ga-DOTA-TATE), where DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, is routinely used for imaging of somatostatin receptor (SST)-expressing tumors. We investigated copper-61 (61Cu) as an alternative radiometal for PET imaging of SST-expressing tumors. Compared to gallium-68, copper-61 (t1/2=3.33 h, Eß + max = 1.22 MeV) can be produced on a large scale, enables late time point imaging, and has the therapeutic twin copper-67. Herein, DOTA-TOC and 1,4, 7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA)-TOC were labeled with copper-61 and compared with the clinically used [68Ga]Ga-DOTA-TOC. Methods: [61Cu]CuCl2 was produced from an irradiated natural nickel target. DOTA-TOC and NODAGA-TOC were labeled with [61Cu]CuCl2 in ammonium acetate buffer so to achieve a reaction pH of 5-6 and a temperature of 95°C for DOTA-TOC or room temperature for NODAGA-TOC. The radioligands were evaluated head-to-head in vitro using human embryonic kidney (HEK)-SST2 cells (affinity, binding sites, cellular uptake, and efflux) and in vivo using HEK-SST2 xenografts [PET/computed tomography (CT) imaging, biodistribution, and pharmacokinetics] and compared with [68Ga]Ga-DOTATOC, which was prepared using a standard procedure. Dosimetry estimates were made for [61Cu]Cu-NODAGA-TOC. Results: [61Cu]Cu-DOTA-TOC and [61Cu]Cu-NODAGA-TOC were prepared at an apparent molar activity of 25 MBq/nmol with radiochemical purities of ≥96% and ≥98%, respectively. In vitro, both presented a sub-nanomolar affinity for SST2 (IC50 = 0.23 and 0.34 nM, respectively). They were almost entirely internalized upon binding to SST2-expressing cells and had similar efflux rates at 37°C. In vivo, [61Cu]Cu-DOTA-TOC and [61Cu]Cu-NODAGATOC showed the same accumulation in SST2-expressing tumors. However, PET/CT images and biodistribution analyses clearly showed an unfavorable biodistribution for [61Cu]Cu-DOTA-TOC, characterized by accumulation in the liver and the abdomen. [61Cu]Cu-NODAGA-TOC displayed favorable biodistribution, comparable with [68Ga]Ga-DOTA-TOC at 1 h post-injection (p.i.). Notwithstanding, [61Cu]Cu-NODAGA-TOC showed advantages at 4 h p.i., due to the tumor retention and improved tumor-to-non-tumor ratios. The effective dose (2.41 × 10-3 mSv/MBq) of [61Cu]Cu-NODAGA-TOC, but also the dose to the other organs and the kidneys (9.65 × 10-2 mGy/MBq), suggested a favorable safety profile. Conclusion: Somatostatin receptor 61Cu-PET imaging not only matches the performance of 68Ga-PET at 1 h p.i. but has advantages in late-time imaging at 4 h p.i., as it provides improved tumor-to-non-tumor ratios. [61Cu]Cu-NODAGATOC is superior to [61Cu]Cu-DOTA-TOC in vivo. The use of the chelator NODAGA allows quantitative labeling with copper-61 at room temperature and enables the straightforward use of a kit formulation for simple manufacturing in medical centers. [ABSTRACT FROM AUTHOR]

Background: Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway. Methods: We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis. Results: The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention. Conclusion: Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome. [ABSTRACT FROM AUTHOR]

Repair of the damaged meniscus is a scientific challenge owing to the poor self-healing potential of the white area of the meniscus. Tissue engineering provides a new method for the repair of meniscus injuries. In this study, we explored the superiority of 2% hyaluronic acid chitin hydrogel in temperature sensitivity, in vitro degradation, biocompatibility, cell adhesion, and other biological characteristics, and investigated the advantages of hyaluronic acid (HA) and Transforming Growth Factor β1 (TGF-β1) in promoting cell proliferation and a matrix formation phenotype. The hydrogel loaded with HA and TGF-β1 promoted cell proliferation. The HA + TGF-β1 mixed group showed the highest glycosaminoglycan (GAG) content and promoted cell migration. Hydroxypropyl chitin (HPCH), HA, and TGF-β1 were combined to form a composite hydrogel with a concentration of 2% after physical cross-linking, and this was injected into a rabbit model of a meniscus full-thickness tear. After 12 weeks of implantation, the TGF-β1 + HA/HPCH composite hydrogel was significantly better than HPCH, HA/HPCH, TGF-β1 + HPCH, and the control group in promoting meniscus repair. In addition, the new meniscus tissue of the TGF-β1 + HA/HPCH composite hydrogel had a tissue structure and biochemical content similar to that of the normal meniscus tissue. [ABSTRACT FROM AUTHOR]

Background: Epilepsy, a common neurological disorder, has been increasingly associated with neuroinflammation, especially microglia activation. To gain insights into the research trends and patterns in this intersection, we conducted a bibliometric analysis of studies published between 2005 and 2024. Using the Web of Science Core Collection, we identified 1,229 relevant articles and reviews, focusing on the relationship between epilepsy and microglia. Methods: We employed the Bibliometrix R package and VOSviewer to analyze the data. Our search strategy combined epilepsy-related terms with microglia and microglial cell keywords. The analysis encompassed publication trends, country and institutional contributions, journal sources, authors, keywords, and thematic evolution. Results: The number of publications has steadily increased, particularly after 2019, indicating growing research interest. The United States, China, and Germany emerged as the most productive countries, with extensive collaboration between China and the United States. Epilepsia and Journal of Neuroinflammation were the most influential journals. Aronica E, Vezzani A, and Engel T were the most prolific authors. Thematic analysis revealed clusters focused on temporal lobe epilepsy, epilepsy-related disorders, and microglia activation. Over the past several years, research has shifted from fundamental brain function studies to in-vivo investigations of specific molecular mechanisms. The CSTB (-) mouse model and NF-κB signaling pathway both merit further in-depth investigation. Conclusion: In conclusion, this bibliometric study reveals a surge in epilepsymicroglia research, led by key countries, journals, and researchers. Temporal lobe epilepsy, epilepsy-related disorders, and microglia activation are focal themes. Future directions include exploring microglia activation mechanisms, utilizing animal models, and interdisciplinary approaches. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease, with an increasing prevalence. Currently, there is no ideal diagnostic molecular imaging agent for diagnosing AD. Antibodies (Abs) have been proposed to close this gap as they can bind selectively and with high affinity to amyloid β (Aβ)--one of the molecular hallmarks of AD. Abs can even be designed to selectively bind Aβ oligomers or isoforms, which are difficult to target with small imaging agents. Conventionally, Abs must be labeled with long-lived radionuclides which typically results in in high radiation burden to healthy tissue. Pretargeted imaging could solve this challenge as it allows for the use of short-lived radionuclides. To develop pretargeted imaging tools that can enter the brain, AD mouse models are useful as they allow testing of the imaging approach in a relevant animal model that could predict its clinical applicability. Several mouse models for AD have been developed with different characteristics. Commonly used models are: 5xFAD, APP/PS1 and tg-ArcSwe transgenic mice. In this study, we aimed to identify which of these models were best suited to investigate pretargeted imaging approaches beyond the blood brain barrier. We evaluated this by pretargeted autoradiography using the Aβ-targeting antibody 3D6 and an 111In-labeled Tz. Evaluation criteria were target-to-background ratios and accessibility. APP/PS1 mice showed Aβ accumulation in high and low binding brain regions and is as such less suitable for pretargeted purposes. 5xFAD and tg-ArcSwe mice showed similar uptake in high binding regions whereas low uptake in low binding regions and are better suited to evaluate pretargeted imaging approaches. 5xFAD mice are advantaged over tg-ArcSwe mice as pathology can be traced early (6 months compared to 18 months of age) and as 5xFAD mice are commercially available. [ABSTRACT FROM AUTHOR]

Purpose: We present a probabilistic approach to medical image analysis that requires, and makes use of, explicit prior information provided by a medical expert. Depending on the choice of prior model the method can be used for image enhancement, analysis, and segmentation. Methods: The methodology is based on a probabilistic approach to medical image analysis, that allows integration of 1) arbitrarily complex prior information (for which realizations can be generated), 2) information about a convolution operator of the imaging system, and 3) information about the noise in the reconstructed image into a posterior probability density. The method was demonstrated on positron emission tomography (PET) images obtained from a phantom and a patient with lung cancer. The likelihood model (multivariate log-normal) and the convolution operator were derived from phantom data. Two examples of prior information were used to show the potential of the method. The extended Metropolis-Hastings algorithm, a Markov chain Monte Carlo method, was used to generate realizations of the posterior distribution of the tracer activity concentration. Results: A set of realizations from the posterior was used as the base of a quantitative PET image analysis. The mean and variance of activity concentrations were computed, as well as the probability of high tracer uptake and statistics on the size and activity concentration of high uptake regions. For both phantom and in vivo images, the estimated images of mean activity concentrations appeared to have reduced noise levels, and a sharper outline of high activity regions, as compared to the original PET. The estimated variance of activity concentrations was high at the edges of high activity regions. Conclusions: The methodology provides a probabilistic approach for medical image analysis that explicitly takes into account medical expert knowledge as prior information. The presented first results indicate the potential of the method to improve the detection of small lesions. The methodology allows for a probabilistic measure of the size and activity level of high uptake regions, with possible long-term perspectives for early detection of cancer, aswell as treatment, planning, and follow-up. [ABSTRACT FROM AUTHOR]

Vitamin A is essential for poultry health, influencing vision, growth, antioxidant defense, reproduction, and immune function. However, it is highly sensitive to degradation when exposed to light, moisture, heat, and oxygen. To address this, vitamin A is typically formulated as retinyl acetate in small beadlets. These beadlets are commonly included in premixes for industrial poultry diets. However, variations in beadlet formulations among different producers can lead to differences in stability and bioavailability, potentially impacting their effectiveness and biological value for poultry. Understanding the stability and bioavailability of various vitamin A sources is crucial for optimizing poultry feeding strategies and ensuring adequate vitamin A supply. The stability of vitamin A can be evaluated through several methods, including premix stability, stability during pelleting, storage stability in feed, and the stability of pure vitamin A products. Bioavailability, which reflects how effectively vitamin A is absorbed and utilized by the animal, is typically assessed through in vivo studies, with liver retinol levels serving as a key indicator. To enhance poultry production, it is important to select vitamin A sources that offer both high stability and bioavailability. Effective feed management, including the use of stable and readily absorbed forms of vitamin A, can improve poultry health, growth rates, and overall production efficiency. [ABSTRACT FROM AUTHOR]

Single-photon emission computed tomography (SPECT) systems with pinhole collimators are becoming increasingly important in clinical and preclinical nuclear medicine investigations as they can provide a superior resolution-sensitivity tradeoff compared to conventional parallel-hole and fanbeam collimators. Previously, open-source software did not exist for reconstructing tomographic images from pinhole-SPECT datasets. A 3D SPECT system matrix modelling library specific for pinhole collimators has recently been integrated into STIR, an open-source software package for tomographic image reconstruction. The pinhole-SPECT library enables corrections for attenuation and the spatially variant collimator-detector response by incorporating their effects into the system matrix. Attenuation correction can be calculated with a simple single line of response or a full model. The spatially variant collimator-detector response can be modelled with a point spread function and depth of interaction corrections for increased system matrix accuracy. In addition, improvements to computational speed and memory requirements can be made with image masking. This work demonstrates the flexibility and accuracy of STIR's support for pinhole-SPECT datasets using measured and simulated single-pinhole SPECT data from which reconstructed images were analysed quantitatively and qualitatively. The extension of the opensource STIR project with advanced pinhole-SPECT modelling will enable the research community to study the impact of pinhole collimators in several SPECT imaging scenarios and with different scanners. [ABSTRACT FROM AUTHOR]

Regeneration is the remarkable phenomenon through which an organism can regrow lost or damaged parts with fully functional replacements, including complex anatomical structures, such as limbs. In 2019, Development launched its 'Model systems for regeneration' collection, a series of articles introducing some of the most popular model organisms for studying regeneration in vivo. To expand this topic further, this Perspective conveys the voices of five expert biologists from the field of regenerative biology, each of whom showcases some less well-known, but equally extraordinary, species for studying regeneration. [ABSTRACT FROM AUTHOR]

Simple Summary: Animal models are crucial for exploration of the causes of and potential treatments for squamous cell carcinoma, a common type of skin cancer. This study compared four different hairless mouse models to determine which is most suitable for studying skin cancer development when exposed to ultraviolet (UV) light. The models varied in their skin characteristics, such as the presence of melanin, cholesterol level, and immune system function. By monitoring various skin health parameters and analyzing proteasome activity, this study found that the SKH-hr2+ApoE and SKH-hr2 models were the most effective for further research into squamous cell carcinoma. In contrast, the SKH-hr1 model, despite its common use, was less suitable. These findings will help guide future research efforts in understanding and developing treatments for skin cancer. Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis. [ABSTRACT FROM AUTHOR]